Novel cytotoxic exhibition mode of antimicrobial peptide anoplin in MEL cells, the cell line of murine Friend leukemia virus‐induced leukemic cells
Novel cytotoxic exhibition mode of antimicrobial peptide anoplin in MEL cells, the cell line of murine Friend leukemia virus‐induced leukemic cells
复制标题
DOI：
10.1002/psc.2533
复制
发表时间：
2013-07
影响因子：
2.1
通讯作者：
Li-Na Zhu;Cai-Yun Fu;Shi-fu Zhang;Wei Chen;Yuanting Jin;Fu-Kun Zhao
中科院分区：
文献类型：
--
作者：
Li-Na Zhu;Cai-Yun Fu;Shi-fu Zhang;Wei Chen;Yuanting Jin;Fu-Kun Zhao
Anoplin是最近从samariensis anplius蜘蛛的毒液囊中分离到的一种抗菌肽（AMP），是迄今为止天然发现的最短的α -螺旋AMP之一，仅由十个氨基酸组成。以往的研究结果表明，anoplin具有较强的抗菌活性，但溶血活性较弱。在本研究中，我们合成了anoplin，研究了其对Friend病毒诱导的白血病细胞（小鼠红细胞白血病（MEL）细胞）的细胞毒性，并提出了其可能的机制。结果表明，anoplin可以通过破坏细胞膜的完整性，以剂量依赖性和时间依赖性的方式抑制MEL细胞的增殖，这表明anoplin发挥了其细胞毒性作用。此外，MEL细胞的细胞周期分布在G0/G1期被明显阻滞。然而，anoplin不能诱导MEL细胞明显凋亡，也不能诱导正常小鼠骨髓细胞形态和数量的明显变化。所有这些结果表明，一般认为，anoplin是一种选择性AMP，是设计安全治疗剂的价值特征。anoplin对MEL细胞的细胞毒性主要是由于质膜的扰动以及细胞周期阻滞等胞内事件。虽然这是一项初步的研究，探索了anoplin在体外而不是体内的活性，但随着传统化疗耐药性的增加，毫无疑问，anoplin作为一种新型的选择性抗癌药物具有理想的特性。版权所有©2013欧洲多肽协会和John Wiley & Sons， Ltd
Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest α‐helical AMP found naturally to date consisting of only ten amino acids. Previous results showed that anoplin exhibits potent antimicrobial activity but little hemolytic activity. In this study, we synthesized anoplin, studied its cytotoxicity in Friend virus‐induced leukemia cells [murine erythroleukemia (MEL) cells], and proposed its possible mechanism. Our results showed that anoplin could inhibit the proliferation of MEL cells in a dose‐dependent and time‐dependent manner via disrupting the integrity of cell membrane, which indicated that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle distribution of MEL cells was arrested in the G0/G1 phase significantly. However, anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could not induce visible changes on morphology and quantity in the bone marrow cells isolated from normal mice. All of these results indicate that anoplin, as generally believed, is a selective AMP, a value characteristic in the design of safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly attributable to the plasma membrane perturbation and also to the intracellular events such as the arrest of cell cycle. Although this is an initial study that explored the activity of anoplin in vitro rather than in vivo, with the increasing resistance of conventional chemotherapy, there is no doubt that anoplin has desirable feature to be developed as a novel and selective anticancer agent. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.